Microwave-assisted synthesis and anti-inflammatory activity evaluation of some novel α-aminophosphonates

Article abstract of DOI:10.1080/10426507.2017.1331233

Anexpeditious green synthetic approach was developed for the synthesis of α-aminophosphonates in good yields through one-pot three component reaction (Kabachnik-Fields reaction) of equimolar quantities of N-(4-amino-2-phenoxy phenyl)methanesulfonamide, di

Full text of DOI:10.1080/10426507.2017.1331233

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Microwave-assisted synthesis and anti-
inflammatory activity evaluation of some novel α-
aminophosphonates
B. Sujatha, S. Mohan, Ch. Subramanyam & K. Prasada Rao
To cite this article: B. Sujatha, S. Mohan, Ch. Subramanyam & K. Prasada Rao (2017):
Microwave-assisted synthesis and anti-inflammatory activity evaluation of some novel α-
aminophosphonates, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2017.1331233
To link to this article: http://dx.doi.org/10.1080/10426507.2017.1331233
Accepted author version posted online: 24
May 2017.
Submit your article to this journal
Article views: 2
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [The UC San Diego Library]
Date: 27 May 2017, At: 04:26

ACCEPTED MANUSCRIPT
Synthesis and bioactivity evaluation of some novel α-aminophosphonates
MICROWAVE-ASSISTED SYNTHESIS AND ANTI-INFLAMMATORY ACTIVITY
EVALUATION OF SOME NOVEL α-AMINOPHOSPHONATES
B. Sujatha1, S. Mohan2, Ch. Subramanyam2, K. Prasada Rao2,*
1Department of Chemistry, Y. A. Govt. Degree College for Women, Chirala-523155, India
2Department of Chemistry, Bapatla Engineering College, Bapatla - 522101, India
*Corresponding author Tel: +918008514677, E-mail address: prasad17467@gmail.com
ABSTRACTS
An expeditious green synthetic approach was developed for the synthesis of α-
aminophosphonates in good yields through one-pot three component reaction (Kabachnik-Fields
reaction) of equimolar quantities of N-(4-amino-2-phenoxy phenyl)methanesulfonamide,
diethylphosphite and various aldehydes under conventional as well as microwave irradiation
1
13
methods. The newly synthesized compounds were characterized by NMR (31P, H and C),
Mass, IR and C, H, N analyses. The synthesized compounds were screened for their anti-
inflammatory activity using rat paw edema method. Most of the compounds from the series
showed good anti-inflammatory activity when compared with standard drug. Especially the
compounds 5d bearing 4-hydroxy-3-nitrophenyl moiety, 5e bearing 3-bromo-4-fluorophenyl
moiety, 5g incorporated with 2,4-dichlorophenyl moiety and 5f containing 4-chlorophenyl
moiety exhibiting edema inhibition of 91.01 to 85.39% after 4 h of carrageenan injection while
the other compounds displayed inhibition ≥75%.
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Graphical Abstract
Keywords
α-aminophosphonates, Kabachnik-Fields reaction, microwave irradiation, anti-inflammatory
activity.
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
INTRODUCTION
The area of drug discovery and drug development has experienced significant advances with the
introduction of combinatorial chemistry approaches.1 This innovative technology of producing
libraries of structurally related compounds is particularly beneficial in the step of lead
optimization. Lead optimizations involves structural modifications of a “lead” compound that
has demonstrated desired biological or pharmacological activities and/or reduce unwanted side
effects.1
Cyclooxygenases (COX-1 and COX-2) have been introduced as novel targets for anti-
inflammatory and cancer treatment during the past few years.2 At present, there is an increasing
body of evidence stating that targeting COX enzymes, especially COX-2 isoform, is an effective
move towards the prevention or treatment of inflammation and various types of cancers.
Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with
analgesic and antipyretic properties.3 But the continuous use of nimesulide can cause diarrhea,
vomiting, skin rash, dizziness and bitterness in the mouth.3 Hence there is a need for developing
superior anti-inflammatories with a better safety profile.
The α-aminophosphonates, structural analogues of natural amino acids have received widespread
attention in medicinal, bioorganic and organic chemistry. They have been reported to show a
wide range of biological activity including antitumor,4 anti-inflammatory5 and antibiotic6
activities. They also used as good enzyme inhibitors,7 herbicides,8 peptide mimetics,9
fungicides,10 insecticides11 plant growth regulators.12 The assortment of possibilities for the
practical use of α-aminophosphonates has stimulated considerable interest toward α-
aminophosphonate chemistry. Various synthetic protocols have been described for the synthesis
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
of α-aminophosphonates. The nucleophilic addition of phosphites to imines (Kabachnik--Fields
reaction) represents a convenient route for their preparation. A variety of Brønsted acid13a or
Lewis acids like ZnCl2,13b BF3-Et2O,13c CdI2/benzene,13d CdI2/microwave13e have been used for
the synthesis of these compounds.
Recently, three-component one-pot syntheses of α-aminophosphonates have been carried out in
organic solvents using lanthanide triflate,14a InCl3,14b ZrCl4,14c In(OTf)3/MgSO4,14d GaI3,14e
BiCl3,14f Cu(OTf)2,14g SbCl3/Al2O3.14h Moreover, water15 and ionic liquid16 turned to be a kind of
promising medium for such three component syntheses of α-aminophosphonates. Solvent-free
transformations of diethylphosphite to α-aminophosphonates could be accomplished in the
presence of LiClO4-Et2O,17a,b TFA,17c LiClO4,17d metal triflate,17e Na2CaP2O7 17f, ZrOCl2.8H2O or
ZrO(ClO4)2.6H2O,17g TsCl.17h
However, many of these catalysts are expensive, highly corrosive, and involve tedious separation
procedures and also require prolonged reaction times. Therefore, the development of a simple,
convenient and an efficient protocol using inexpensive and readily available reagents would
extend the scope of the synthesis of α-amino phosphonates. Further, in recent years the use of a
microwave irradiation technique18a,b,c has played a prominent role to promote one-pot synthesis
of α-aminophosphonates and offer a number of advantages over the standard heating techniques
such as enhanced reaction yield, shorten the reaction time and easy work-up procedure. To make
this process more efficient, we herein describe the synthesis of some novel α-aminophosphonates
with different species of aldehydes, N-(4-amino-2-phenoxy phenyl)methanesulfonamide and
diethylphosphite under conventional as well as microwave assisted methods.
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
RESULTS AND DISCUSSION
A series of α-aminophosphonates (5a-j) were conveniently synthesized by the reaction of
equimolar quantities of N-(4-amino-2-phenoxy phenyl)methanesulfonamide (2, 0.005 mol)
which is previously prepared from nimesulide (1) on reduction, diethylphosphite (3, 0.005 mol)
and various aldehydes (4a-j) (0.005 mol) through Kabachnik-Field reaction under conventional
and microwave irradiation methods using neat reaction conditions was depicted in Scheme 1.
The physical data of the title compounds are given in Table S 1 (Supplemental materials).
The chemical structure of the title compounds 5a-j are supported by spectral data (31P, 1H and 13C
NMR IR and LC-MS), elemental analysis and the results are presented in Experimental section.
31P NMR signals were observed in the region 18.5-16.8 ppm19 for all the compounds 5a--j. The
1H NMR spectra gave signals due to Ar-H in the range of δ 8.18-6.33 ppm. The proton signals in
the range of 8.54-8.41, 5.33-5.29 and 4.56-4.49 ppm were due to SO2-NH, C-NH and P-CH
respectively. The methylene protons of P-O-CH2CH3 gave a multiplet and methyl protons of P-
O-CH2CH3 resonated as a triplet in the region δ 3.88-3.85 and δ 1.27-1.22 respectively. 13C
NMR chemical shift for P-CH and OCH3 were observed in the region 56.1-55.4 and 38.2-37.6
ppm. 13C NMR chemical shifts were observed in the regions, δ 64.5-64.4 and 16.8-16.3 ppm for
P-O-CH2-CH3 and P-OCH2-CH3 respectively in the title compounds. IR absorptions in the
regions 3399-3389, 3288-3279 and 1229-1222cm1 were assigned to SO2-NH, NH and P = O
stretching vibrations respectively for the compounds 5a-j. In their mass spectra, M+. ions were
13
31
observed in the expected m/z values. Representative spectra (1H, C, P) NMR, mass and IR
spectra for the new compounds 5a, 5d, 5f and 5j are presented in the Supplemental Materials
(Fig. S 1--S 20).
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Biology
Anti-inflammatory activity
In order to identify the potential anti-inflammatory agents among the newly synthesized
compounds we evaluated them for their in vivo anti-inflammatory activity using carrageenan-
induced paw edema method20 in rats.
A careful study of the results shown in Table S 2 revealed that most of the compounds showed
significant anti-inflammatory activity 3 h and 4 h after carrageenan injection. A total of 5
compounds showing more than 80% inhibition after 3 h (as compared to the reference drugs
88.34 & 85.88%) and 7 compounds showing more than 80% inhibition after 4 h (as compared to
the references drug 91.57% & 88.20%). Compounds 5d (R = 4-OH, 3-NO2), 5e (R = 3-Br, 4-F),
5g (R = 2,4-Cl), 5f (R = 4-Cl), and 5b (R = 3-NO2) showed remarkable anti-inflammatory
activity ranging from 87.73% to 84.04% which is comparable to the reference drug Diclofenac
sodium (88.34%) and Nimesulide (85.88%), 3 h after carrageenan injection. The compounds 5j
(R = 5-nitrothiophen-2-yl), 5a (R = 4-F), 5i (R = thiophen-2-yl), 5c (R = 3-NO2, 4-Cl) and 5h (R
= 2-OH) showed appreciable anti-inflammatory activity ranging from 79.75% to 74.84%, 3 h
after carrageenan injection. Similarly compounds 5d (R = 4-OH, 3-NO2), 5e (R = 3-Br, 4-F), 5g
(R = 2,4-Cl), 5f (R = 4-Cl), and 5b (R = 3-NO2), 5a (R = 4-F) and 5j (5-nitrothiophen-2-yl)
showed anti-Inflammatory activity ranging from 91.01% to 80.33% inhibition, 4 h after
carrageenan injection. The remaining compounds showed anti-Inflammatory activity ranging
from 78.08% to 75.84% inhibition, 4 h after carrageenan injection (Fig. S 21). It is difficult to
draw a correlation between the anti-inflammatory activity and the substituents present on the
aromatic rings in 1 or 2 as the anti-inflammatory activity seems to be independent of the nature
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
of substituents. Overall majority of the title compounds exhibited good anti-inflammatory
activity when compared with the reference drugs (Table S 2).
EXPERIMENTAL
All the chemicals are procured from Sigma-Aldrich, Merck and Lancaster were used as such
without further purification. All solvents used for spectroscopic and other physical studies were
reagent grade and were further purified employing the reported methods. The melting points
were determined in open capillary tubes on a Guna Digital Melting Point apparatus and are
uncorrected. IR spectra (νmax in cm1) were recorded as KBr pellets using Perkin-Elmer
1
13
31
spectrophotometer at University of Hyderabad, Hyderabad. The H, C and P NMR Spectra
were recorded on Bruker AMX spectrometer operating at 400 MHz for 1H, 100 MHz for 13C and
161.9 MHz for 31P NMR. All compounds were dissolved in DMSO-d6 and chemical shifts were
referenced to TMS (1H and 13C NMR) and 85% H3PO4 (31P NMR) and Mass spectra were
recorded on API 2000 Perkin-Elmer PE-SCIEX Mass spectrometer. Micro-analytical data were
obtained from University of Hyderabad, Hyderabad, India.
Preparation of N-(4-amino-2-phenoxy phenyl)methanesulfonamide21 (2).
In the first step, to a mixture of nimesulide (5.00 g, 16.2 mmol) and tin (3.13 g) was
added conc. HCl (20 mL) and the mixture was heated on a water bath at 90 C for 3h. After the
completion of the reaction, the mixture was poured into ice water and the solid separated was
filtered. After basification the crude product obtained was purified by re-crystallization from
methanol and chloroform mixture to give the desired product as light brown solid; mp 198 C;
IR (KBr) νmax/ cm1: 3412, 1572, 1487, 1215 and 1154; 1H NMR (400 MHz, DMSO-d6) δ 9.2 (s,
1H), 7.4 (m, 2H), 7.3 (d, J 8.6 Hz, 1H), 7.2 (m, 2H), 6.8 (d, J 8.6 Hz, 1H), 6.5 (s, 1H), 3.5 (br s,
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2H), 3.1 (s, 3H); Mass (m/z): 279.1 (M+, 100%); Elemental analysis found C, 56.25; H, 5.07; N,
10.26; C13H14N2O3S requires C, 56.10; H, 5.07; N, 10.06.
Procedure for the synthesis of α-aminophosphonates 5a-j
Conventional method:
A mixture of N-(4-amino-2-phenoxy phenyl)methanesulfonamide (2, 0.005 mol) in ethanol,
diethylphosphite (3, 0.005 mol) and 4-fluorobenzaldehyde (4a, 0.005 mol) were taken in flat-
bottomed flask and stirred the reaction mixture vigorously at 40 C for 4 h. The reaction progress
was monitored by TLC on silica gel using ethyl acetate-hexane (7:3 v/v). After completion of the
reaction, the solvent was removed under reduced pressure to get the crude product. The resulting
crude product was purified by column chromatography on silica gel (100-200 mesh) using ethyl
acetate-hexane (1:1) as eluent to afford pure diethyl (4-fluorophenyl)(4-(methylsulfonamido)-3-
phenoxyphenylamino)methylphosphonate (5a). The other compounds 5b-j were prepared by
adapting to the above described procedure.
Microwave irradiation method:
A
mixture of N-(4-amino-2-phenoxy phenyl)methanesulfonamide (2, 0.005 mol),
diethylphosphite (3, 0.005 mol) and 4-fluorobenzaldehyde (4a, 0.005 mol) were taken in flat-
bottomed flask and irradiated with microwave radiations in a microwave oven at 490 W. The
reaction mixture was heated successively twice for 2-3 min period each time followed by a 1 min
cooling interval between irradiations. This method was intended to avoid continuous overheating
of the reactants. The reaction mixtures were kept under stirring to maintain the homogeneity of
the irradiating field throughout the reaction. By monitoring with TLC, the reaction was stopped
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
after 3-6 min. The obtained crude products were recrystallized from ethyl acetate to afford pure
5a-j as solids with 80.9-90.6% yield.
Physical, analytical and spectral data for the compounds (5a-j)
Diethyl
(4-fluorophenyl)(4-(methylsulfonamido)-3-phenoxyphenylamino)methanephosph-
onate (5a):
Yield: 90%; solid. 31P NMR spectrum (DMSO-d6): δ 18.5 ppm; 1H NMR spectrum (DMSO-d6):
δ 8.41 (s, 1H, SO2-NH), 7.68-7.23 (m, 9H, Ar-H), 6.54 (d, J = 8.0 Hz, 1H, Ar-H), 6.49 (d, J =
6.8 Hz, 1H, Ar-H), 6.33 (s, 1H, Ar-H), 5.33 (s, 1H, C-NH), 4.55 (d, 1H, P-CH), 3.88 (m, 4H, O-
CH2CH3), 2.89 (s, 3H, SO2CH3), 1.27 (t, J = 5.6 Hz, 6H, O-CH2CH3); 13C NMR spectrum
(DMSO-d6): δ 161.9, 157.8, 141.5, 136.5, 132.8, 129.7, 127.6, 122.5, 121.5, 119.9, 118.3, 114.3,
113.6, 101.9, 64.4, 55.8, 37.9, 16.5; IR (KBr) (νmax cm1): 3407 (SO2-NH), 3296 (NH), 1227 (P
= O); LCMS (m/z, %): 523 (M+H+, 100); Anal. Calcd for C24H28FN2O6PS: C, 55.17; H, 5.40; N,
5.36%; found: C, 55.54; H, 5.38; N, 5.42%.
Diethyl (4-chlorophenyl)(4-(methylsulfonamido)-3-phenoxyphenylamino) methanephosph-
onate (5f):
Yield: 81%; solid. 31P NMR spectrum (DMSO-d6): δ 17.6 ppm; 1H NMR spectrum (DMSO-d6):
δ 8.41 (s, 1H, SO2-NH), 7.68-7.22 (m, 9H, Ar-H), 6.54 (d, J = 8.0 Hz, 1H, Ar-H), 6.49 (d, J =
6.8 Hz, 1H, Ar-H), 6.33 (s, 1H, Ar-H), 5.33 (s, 1H, C-NH), 4.55 (d, 1H, P-CH), 3.88 (m, 4H, O-
CH2CH3), 2.89 (s, 3H, SO2CH3), 1.27 (t, J = 5.6 Hz, 6H, O-CH2CH3); 13C NMR spectrum
(DMSO-d6): δ 157.8, 141.5, 136.5, 135.1, 134.2, 129.9, 129.4, 127.6, 122.5, 121.5, 119.9, 118.3,
113.6, 101.9, 64.4, 55.7, 37.6, 16.4; IR (KBr) (νmax cm1): 3399 (SO2-NH), 3285 (NH), 1227 (P
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
= O); LCMS (m/z, %): 539 (M+H+, 100), 541 (M+2, 38); Anal. Calcd for C24H28ClN2O6PS: C,
53.48; H, 5.24; N, 5.20%; found: C, 53.52; H, 5.20; N, 5.15%.
Anti-inflammatory activity
Anti-inflammatory activity of newly synthesized compounds was evaluated in vivo using
carrageenan-induced paw edema method19 in rats. Majority of the title compounds exhibited
good anti-inflammatory activity when compared to the standard drugs (Table S 2).
CONCLUSION
In conclusion, in an attempt of developing a new class of anti-inflammatory agents, a new series
of α-aminophosphonates has been prepared using a green and an efficient solvent-free procedure
under conventional and microwave irradiation methods. The excellent yields of α-
aminophosphonates were obtained in microwave irradiation method in short reaction times. Anti-
inflammatory screening results of 5a-j showed that most of the derivatives markedly reduced the
paw edema volume in the immediate one hour of administration and the inhibitory effect was
regularly increasing from the administration time to the end of 4th hour. It was found to be most
significant at 3 h and 4h. Overall looking at duration of action and percent inhibition, the
sustained and momentous action was reported with 5d, 5e, 5g, 5f, 5b, 5a and 5j. Hence the
present series could be developed as a novel class of anti-inflammatory agents.
ACKNOWLEDGMENTS
The authors acknowledge Dr. Sk. Adam, department of biochemistry, Sri Venkateswara
University, Tirupathi, India, for providing biological activity. Also, the authors express their
thanks to Hyderabad Central University for providing instrumentation facilities for recording the
spectra.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
REFERENCES
1. Bin, Su.; Darby, M. V.; Brueggemeier, R. W. J. Comb Chem. 2008, 10, 475-483.
2. Xie, W.; Robertson, D. L.; Simmons, D. L. Drug Dev. Res. 1992, 25, 249-265.
3. Thawani, V.; Sontakke, S.; Gharpure, K.; Pimpalkhute, S. Indian J. Pharmacol. 2003, 35,
121-122.
4. Craig, J. C.; Person, P. E. J. Med. Chem. 1971, 14, 1221.
5. Sukhova, N. M.; Lidak, M.; Zidermane, A.; Pelevina, I. S.; Voronia, S. S. Khim.-Farm.
Zh. 1989, 23, 1226-1229.
6. Subramanyam, Ch.; Thaslim Basha, Sk.; Madhava, G.; Nayab Rasool, Sk.; Adam, Sk.;
Durga Srinivasa Murthy S.; Naga raju, C. Phosphorus Sulfur Silicon Relat. Elem. 2017,
192, 267-270.
7. Atherton, F. R.; Hassal, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29-33.
8. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32,
1652-1661.
9. Natchev, I. A. Liebigs Ann. Chem. 1988, 9, 861-867.
10. Kafarski, P.; Lejczak, B. Phosphorus Sulfur Silicon Relat. Elem. 1991, 63, 193-215.
11. Chen, R. Y.; Mao, L. J. Phosphorus Sulfur Silicon Relat. Elem. 1994, 89, 97-104.
12. Maier, L. Phosphorus Sulfur Silicon Relat. Elem. 1990, 53, 43-67.
13. (a) Petov, K.A.; Chauzov, V.A.; Erkhina, T.S. Usp. Khim. 1974, 43, 2045-2087.(b) Zou,
J.; Pol. J. Chem. 1981, 55, 643-646. (c) Laschat, S.; Kunz, H.; Synthesis, 1992, 1, 90-95.
(d) Kabanchnik, M.M.; Ternovskaya, T.N.; Zobnina, E.V.; Beletskaya, I.P.; Russ. J. Org.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Chem. 2002, 38, 480-483. (e) Kabanchnik, M.M.; Zobnina, E.V.; Beletskaya, I.P.; Russ.
J. Org. Chem. 2005, 41, 505-507.
14. (a) Qian, C.; Huang, T.; J. Org. Chem. 1998, 63, 4125-4128. (b) Ranu, B.C.; Hajra, A.;
Jana, U. Org. Lett. 1999, 1, 1141-1143. (c) Yadav, J.S.; Reddy, B.V.S.; Raj, S.; Reddy,
K.B.; Prasad, A.R. Synthesis 2001, 15, 2277-2280. (d) Ghosh, R.; Maiti, S.; Chakraborty,
A.; Maiti, D. J. Mol. Chem. A. 2004, 210, 53-57. (e) Sun, P.P.; Hu, Z.X.; Huang, Z. H.
Synth. Commun. 2004, 34, 4293-4299. (f) Zhan, Z.P.; Li, J.P. Synth. Commun. 2005, 35,
2501-2505. (g) Paraskar, A.S.; Sudalai, A. Arkivoc. 2006, 10, 183-189. (h) Ambica, K.S.;
Taneja, S.C.; Hundal, M.S.; Kapoor, K.K. Tetrahedron Lett. 2008, 49, 2208-2212.
15. Akiyama, T.; Matsuda, M.; Fuchibe, K. Synthesis 2005, 15, 206-209.
16. Yadav, J. S.; Reddy, B.V.S.; Sreedhar, P. Green Chem. 2002, 4, 436-438.
17. (a) Saidi, M.R.; Azizi, N. Synlett 2002, 8, 1347-1349. (b) Azizi, N.; Saidi, M.R.
Tetrahedron 2003, 59, 5329-5332. (c) Akiyama, T.; Sanada, M.; Fuchibe, K. Synlett
2003, 10, 1463-1464. (d) Azizi, N.; Rajabi, F.; Saidi, M. R. Tetrahedron Lett. 2004, 45,
9233-9236. (e) Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis 2004, 16, 2692-2696.
(f) A. Elmakssoudi, M. Zahouily, A. Mezdar, A. Rayadh, S. Sebti, C. R. Chim. 2005, 8,
1954-1959. (g) Bhagat, S.; Chakraborti, A.K. J. Org. Chem. 2008, 73, 6029-6032. (h)
Kaboudin, B.; Jafari, E. Synlett 2008, 12, 1837-1839.
18. (a) Yadav, J.S.; Reddy, B.V.S.; Madan, U. Synlett 2001, 7, 1131-1133. (b) Koboudin, B.;
Nazari, R. Tetrahedron Lett. 2002, 42, 8211-8213. (c) A.K. Battacharya, K.C. Rana,
Tetrahedron Lett. 2008, 49, 2598-2601.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
19. Satish A. D.; Dnyaneshwar S. R.; Kiran R. K.; Rooth S. M.;, Satish U. D.; Rajendra P. P.
Bioorg. Med. Chem. Lett. 2011, 21, 2527--2532.
20. Winter, C. A.; Risley, E. A.; Nuss, G. W. Proc. Soc. Exp. Biol. Med. 1962, 111, 544-547.
21. Pericherla, S.; Mareddy, J.; Rani, D.P.G.; Gollapudi, P. V.; Pal, S.; J. Braz. Chem. Soc.
2007, 18, 384-390.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
NHSO2CH3
O
Microwave irradiation
NHSO2CH3
O
NHSO2CH3
O
O
O
Catalyst free
Solvent free
OC2H5
OC2H5
Sn/ HCl
90 ºC
O
H
P
H
R
P
O
NH
C2H5OH,30-40 ºC
O
NO2
NH2
1
2
3
4a-j
Conventional Conditions
5a-j
R
R
R
R
Compd
Compd
Compd
Br
5a
F
5e
5h
F
HO
NO2
5b
5c
5d
5f
5i
5j
Cl
Cl
S
S
NO2
5g
NO2
Cl
NO2
Cl
OH
Scheme 1: Microwave assisted synthesis of some novel α-aminophosphonates (5a-j)
14
ACCEPTED MANUSCRIPT